Method of servicing companies associated with a spray device operating under guidelines of a regulatory body

ABSTRACT

A method for servicing companies associated with a spray device operating under guidelines of a regulatory body includes capturing in vitro actuation data associated with operation of the spray device and distributing the data to a company associated with an aspect of the spray device. The company may use the data for testing the spray device to ensure continued compliance with prior approval of the spray device by the regulatory body. The method may also include converting the data to parameters and distributing the parameters. Capturing the in vitro actuation data may include sorting the data based on in vitro age groups. Distributing the data may include providing the data in a format executable by an automated actuation system. The company receiving the data may be a drug development company, spray device manufacturer, or testing service. The regulatory body may be the Food and Drug Administration (FDA).

RELATED APPLICATION(S)

This application claims the benefit of U.S. Provisional Application No.60/462,861, filed on Apr. 14, 2003. The entire teachings of the aboveapplication are incorporated herein by reference.

BACKGROUND OF THE INVENTION

A spray pump's performance is characterized in terms of its emittedspray pattern, plume geometry, and/or droplet size distribution. Theseparameters are known to be affected by the means in which the spray pumpis actuated. For example, slow actuation will likely cause pooratomization, producing a stream-like flow. Fast actuation will likelyproduce too fine a spray, leading to poor absorption in the nasal mucosaand unwanted inhalation and deposition of the droplets in the throat andlungs. These factors and others, such as drug compatibility with thespray device, may result in the drug delivery falling outside thecriteria associated with an original clinical trial approval. Testingthe delivery or spray devices may be done to verify the spray deviceactuates the drug within the criteria of the original clinical trialapproval, but operator actuation variability may adversely affect testresults.

SUMMARY OF THE INVENTION

Automated actuation of nasal spray devices subject to in vitrobioequivalence testing may be employed to decrease variability in drugdelivery due to operator factors (including removal of potential analystbias in actuation) and increase the sensitivity for detecting potentialdifferences among drug products. An automated actuation system mayinclude settings for force, velocity, acceleration, length of stroke,and other relevant parameters. Selection of appropriate settings isrelevant to proper usage of the product by a trained patient, and, fornasal sprays, may be available from pump suppliers for tests such asdroplet size distribution by laser diffraction or spray patternphotographic techniques. In the absence of recommendations from the pumpsupplier, settings may be documented based on exploratory studies inwhich the relevant parameters are varied to simulate in vitroperformance upon hand actuation. Exploratory studies of hand actuationof the spray pump device are useful to determine appropriate settingsfor automated actuation.

Accordingly, one embodiment of the principles of the present inventionincludes an assembly that provides information about operation of aspray device. The assembly includes an adapter assembly configured to becoupled to a movable part of the spray device. In the case of a nasalspray, the movable part is the nasal tip and, in the case of a MeteredDose Inhaler (MDI), the movable part is the canister containing thedrug. The assembly also includes a mounting assembly configured to becoupled to a stationary part of the spray device. In the case of thenasal spray device, the stationary part is the bottle containing thedrug and, in the case of the MDI, the stationary part is the mouthpiece.The assembly also includes a transducer, coupled to the mountingassembly or the adapter assembly. The assembly also includes a linkagethat is adapted to extend between the mounting assembly and the adapterassembly. The linkage is in operational relationship with the transducerto enable the transducer to indicate a mechanical relationship betweenthe movable and stationary parts of the spray device corresponding tothe operation of the spray device.

The mounting assembly may include a bearing and shaft assembly couplingthe adapter assembly to the mounting assembly. The bearing and shaftassembly may substantially maintain alignment between the adapterassembly and the mounting assembly in non-actuation axes.

The assembly may also include a base assembly adapted to be coupled tothe mounting assembly. The base assembly may include a foot assemblywith a footprint that supports the spray device in a verticalrelationship with the foot assembly. The assembly and spray device mayhave a predetermined weight for use on a weight measuring scalesensitive enough to measure a change in fluid ejected by the spraydevice in a single discharge. In one embodiment, the total weight of theassembly and spray device is less than or equal to 200 grams.

The transducer may be a position sensor. An example of one such positionsensor is a potentiometer. In the case of the potentiometer, the linkageis a spring loaded wire integrally associated with the potentiometer.

The adapter assembly may be configured to interface with an automatedactuation system that operates the spray device in an automated manner.The transducer may indicate the mechanical relationship in a formatusable by the automated actuation system.

The assembly may also include a data processing system coupled to thetransducer that captures indications of the mechanical relationshipbetween the movable part and the stationary part of the spray device.The data processing system may include program instructions thatautomatically calculate parameters in position, velocity, oracceleration corresponding to operation of the spray device. Theinstructions may include a routine that calculates velocity oracceleration data from position measurements using a least squarestechnique. The parameters may include at least one of the following:maximum position displacement, hold time, maximum actuation velocity,maximum return velocity, maximum actuation acceleration, and maximumreturn acceleration. The actuation direction is defined herein as thedirection in which the movable part causes atomization of the liquiddrug contained in the spray device, and the return direction is definedherein as the direction in which the movable part returns to its stateof rest. The data processing system may also include a signalconditioner, data sampler, and amplifier, wherein the signal conditionerconditions a signal effected by the transducer prior to the data samplerand amplifier operating on the signal.

The principles of the present invention include corresponding methodsrelated to the above-described apparatus and alternative embodimentsthereof described below.

Another embodiment according to the principles of the present inventionincludes a method for servicing companies associated with a spray deviceoperating under guidelines of a regulatory body. The method includescapturing in vitro actuation data associated with operation of the spraydevice. The method also includes distributing the data to a companyassociated with an aspect of the spray device. The company may use thedata for testing the spray device to ensure continued compliance withprior approval of the spray device by a regulatory body.

The method may also include converting the data to parameters anddistributing the data in the form of the parameters. The spray devicemay include a stationary part and a movable part, and the data mayrepresent a mechanical relationship between the stationary part and themovable part versus time. The method may also include measuringposition, velocity, or acceleration relationships between the stationarypart and the movable part.

Capturing the in vitro actuation data may include sorting the data basedon in vitro age groups. Capturing the in vitro actuation data may alsoinclude determining a minimum number of priming strokes by handactuation. Further, capturing the in vitro actuation data may includedetermining actuation parameter ranges by hand actuation. Capturing thein vitro actuation data may include determining an initial estimation ofdelivery performance congruency between hand and automated actuation.The method may also include adjusting automated actuation parametersassociated with the automated actuation to achieve a desired shot weightand to determine acceptable ranges.

Distributing the data may include providing the data in a formatexecutable by a machine configured to actuate the spray device in anautomated manner. Prior approval may be a clinical trial approval.

The company receiving the data may be a drug development company, spraydevice manufacturer, or testing service. The regulatory body may be theFood and Drug Administration (FDA).

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other objects, features and advantages of theinvention will be apparent from the following more particulardescription of preferred embodiments of the invention, as illustrated inthe accompanying drawings in which like reference characters refer tothe same parts throughout the different views. The drawings are notnecessarily to scale, emphasis instead being placed upon illustratingthe principles of the invention.

FIG. 1 is an illustration of an example application in which theprinciples of the present invention may be employed;

FIGS. 2A–2B are diagrams of spray devices ejecting an atomized drugproduced by actuation of the spray device containing the drug used inthe application of FIG. 1;

FIG. 3 is a diagram of an assembly connected to the spray device of FIG.1;

FIG. 4 is an alternative embodiment of the assembly of FIG. 3;

FIGS. 5A–5B are side views of the assembly embodiments of FIGS. 3 and 4,respectively;

FIG. 6 is an embodiment of the assembly of FIG. 3 in which a shaft andbearing assembly is employed;

FIG. 7 is a side view of the assembly of FIG. 6;

FIG. 8 is a diagram of an automated actuation system used in theapplication of FIG. 1;

FIG. 9 is a block diagram of a data capture and processing systemadapted to be used with the assembly of FIGS. 3 and 4;

FIG. 10 is an alternative embodiment of the data capture and processingsystem of FIG. 9;

FIG. 11 is a process optionally used with the data capture andprocessing systems of FIGS. 9 and 10;

FIG. 12 is a user interface optionally used with the data capture andprocessing systems of FIGS. 9 and 10;

FIG. 13 is a set of waveform diagrams illustrating captured dataassociated with the spray devices of FIGS. 2A–2B;

FIGS. 14–17 are actual test data associated with in vitro testing andautomated testing of the spray device of FIG. 2A;

FIG. 18A is a model of a business environment in which another aspectaccording to the principles of the present invention related to theapplication of FIG. 1 may be employed;

FIG. 18B is a block diagram including the businesses of FIG. 18Acommunicating via a computer network;

FIG. 19 is a process used in the model of FIG. 18A;

FIG. 20 is a subprocess used in the process of FIG. 19; and

FIG. 21 is a subprocess used in the process of FIG. 20.

DETAILED DESCRIPTION OF THE INVENTION

A description of preferred embodiments of the invention follows.

FIG. 1 illustrates a spray device application in which the principles ofthe present invention may be employed. A person 105 uses a spray device100, such as a nasal spray pump or Metered-Dose Inhaler (MDI), toreceive a drug supplied in a liquid form. In the case of a nasal spraypump, the person 105 uses his hand 115 to actuate the spray device 100to cause the liquid drug to be atomized and projected into a nostril110. In the case of an MDI, the person 105 uses hand actuation toproject an atomized drug into his mouth 120.

It has been observed that different age groups apply different forces tothe spray devices 100. Therefore, a drug development company and/orspray device manufacturer cannot always predict the amount of drug thatwill reach the intended nasal mucosa. A regulatory body, such as theFood and Drug Administration (FDA), may approve a given drug for apredetermined dose. However, spray device manufacturers rarely, if ever,know what the appropriate settings should be for automated actuationtesting. This is primarily due to the fact that the device manufacturersrarely have the requisite knowledge of the physical properties of thedrug formulation (e.g., viscosity and surface tension) because theformulations are proprietary to the drug company. Thus, the spray devicemanufacturers generally do not know how these properties will affect thecharacteristics of the spray the spray device produces when actuated byhand or by an automated actuation system. Additionally, the spray devicemanufacturer may not have the same automated actuation system as thedrug company, thereby further reducing their ability to supply theappropriate actuation settings to the automated actuation system.Moreover, in practice, based on a person's age group, the amount of drugejected (i.e., dosage) from the spray device 100 may be different fromexpected. Therefore, the amount absorbed by the person 105 may bedifferent from what the regulatory body approved in clinical trials,thereby causing concern that a person's response to the drug may bedifferent from the criteria determined to be safe and effective in theclinical trials. Some other factors that affect the amount of drugdischarged by the spray device 100 are atomization rate of the drug,droplet size, spray pattern, plume geometry, priming and re-primingrates, and environmental conditions.

FIGS. 2A and 2B illustrate spray patterns 200 a and 200 b, respectively,produced by the same or different spray devices 100. In FIG. 2A, thespray pattern 200 a is projected in a relatively conical pattern. InFIG. 2B, the drug is more atomized than in FIG. 2A as evidenced by abroader spray pattern 200 b.

Spray pattern studies characterize a spray either during the spray priorto impaction or following impaction on an appropriate target, such as athin-layer chromatography (TLC) plate. Spray patterns for certain nasalspray products may be spoked or otherwise irregular in shape.

Spray patterns can be characterized and quantified by either manual orautomated image analysis. Both analyses allow shape and size to bedetermined. Automated analysis systems may also allow determination ofCenter of Mass (COM) and/or Center of Gravity (COG) within the patternto be determined.

Plume geometry describes a side view of the aerosol cloud parallel tothe axis of the plume. High-speed photography, laser light sheet, andhigh speed digital camera or other suitable methods are generally usedto determine plume geometry.

Priming and re-priming data also ensure delivery of a dosage of drug andare taken into account when measuring spray patterns 200 a and 200 b toaccurately model in vitro operation.

FIG. 3 is an illustration of an example assembly that may be adapted tointerface with the spray device 100. In accordance with the principlesof the present invention, the assembly is adapted to indicate amechanical relationship between a movable part 305 and a stationary partof the spray device 100 corresponding to operation of the spray device100. In a nasal spray pump application, the movable part 305 may bereferred to as a nasal tip since it is inserted into the nostril 110.The stationary part 310 may be referred to as a nasal spray pump bottlein this application.

Components that are connected to the spray device 100 include (a) anadapter assembly 315 a, which connects to the movable part 305, (b) amounting assembly 320 a, which connects to the spray device 100, (c) atransducer 335, which is connected to the mounting assembly 320 a inthis embodiment but may be connected to the adapter assembly 315 a inother embodiments, and (d) a linkage 330, which may be a spring loadeddraw wire that is adapted to extend between the mounting assembly 320 aand adapter assembly 315 a. The linkage 330 is in operationalrelationship with the transducer 335 to enable the transducer 335 toindicate the mechanical relationship between the movable part 305 andthe stationary part 310 of the spray device 100 corresponding tooperation of the spray device 100.

The transducer 335 may be a position sensor, such as a potentiometer.Extending from the potentiometer is a transducer cable 340 providing atransducer output. The transducer cable 340 connects at the other end(not shown) to a data acquisition (DAQ) circuit board (not shown) orother electronics to capture and/or process the transducer output.

The mounting assembly 320 a may be connected to the stationary part 310through use of flexible tie straps 325. Other connection means may alsobe used, such as Velcro® straps, adhesive, or other suitable attachmentmeans. A rubber or other suitable material may be used to form a solidconnection between the adapter assembly 315 a and the movable part 305.Securing of the adapter assembly 315 a or the mounting assembly 320 a tothe respective parts 305, 310 of the spray device 100 may be completedthrough screw means, latching mechanism, or other suitable mechanism.

In this particular embodiment, the draw wire 330 is kept taut enough bythe spring in the transducer 335 to prevent sluggishness withoutdeflecting the movable part 305 of the spray device 100 or the adapterassembly 315 a. The lateral location of the transducer 335 relative tothe mounting assembly 320 a is then adjusted and tightened against themounting assembly 320 a so that the draw wire 330 is parallel to theactuation axis of the spray device 100.

In operation, a person 105 operates the spray device 100 in a typicalmanner by placing his fingers on the adapter assembly 315 a and drawingit toward the mounting assembly 320 a to cause the movable part 305 tomove. The motion produces a “shot” or dosage to the expelled from thespray device 100. When the spray device 100 is actuated, the linkage 330causes the transducer 335 to change its state. A change in state of thetransducer 335 causes the transducer output to change state in aproportional manner. The data acquisition circuit board (not shown)captures the change in state of the transducer 335 and provides thecaptured data to a processor for further processing. Prior to testing,the transducer 335 may be calibrated and used during the processing.

FIG. 4 is an illustration of the components applied to a metered-doseinhaler (MDI) 400. The spray bottle 100 and MDI 400 are interchangeablyreferred to herein as “spray devices”. In the case of the MDI 400, apressurized canister 405 is the movable part, and a mouthpiece 410 isthe stationary part. A person's hand 115 squeezes the pressurizedcanister 405 toward the mouthpiece 410 to actuate the MDI 400 and causea “shot” to be expelled from the MDI 400.

Similar to its usage with the spray bottle 100, the linkage 330 extendsbetween the adapter assembly 315 b and mounting assembly 320 b. Thelinkage 330 causes the transducer 335 to change states, which istransmitted by way of the transducer cable 340 to a data acquisitionsystem or other processor (not shown).

FIGS. 5A and 5B include indications of axes associated with the spraydevices 100 and 400. Referring to FIG. 5A, an actuation axis 505 aextends from the movable part 305, and a draw wire axis 510 a extendsalong the linkage 330. Also indicated in FIG. 5A is a pair of adjustmentslots 520 and corresponding adjustment screws 515 that hold thetransducer 335 (hidden by the mounting assembly 320 a).

In FIG. 5B, the actuation axis 505 b extends vertically from thepressurized canister 405, and the draw wire axis 510 b extends along thelinkage 330.

In both cases of spray devices 100, 400, rotation of the linkage 330about the actuation axis 505 a, 505 b causes the transducer 335 tochange state much faster than normal operation of the spray device 100(i.e., actuation along the actuation axis 505 a, 505 b). Such a rotationof the linkage 330 is possible if the adapter assembly 315 a, 315 bslips (i.e., spins about the actuation axis). Similarly, pivoting of theadapter assemblies 315 a and 315 b causes the linkage 330 to rapidlyaffect the state of the transducer 335. Rapid changes in the output ofthe transducer 335 affects in vitro measurements. Therefore, theassembly described may be improved by having a more rigid connectionbetween the mounting assembly 320 a and the adapter assembly 315 a. Anassembly providing a more rigid connection and, therefore, lessmeasurement error, is illustrated in FIG. 6.

FIG. 6 illustrates an embodiment of an assembly 600 that employs abearing 610 and shaft 605 assembly that substantially maintainsalignment between the adapter assembly 315 c and the mounting assembly320 c. The linkage 330 is extended through the shaft 605 and connects toa shaft head 615 by extending through a center hole in the shaft head615. The linkage 330 may be held in place through use of a slot 630designed for this purpose.

By using the bearing 610 and shaft 605 assembly, the pivoting of themovable part 305 of the spray device 100 is dramatically reduced overthe embodiment of FIG. 3. Further, the assembly 600 may be constructedof lightweight materials, such as aluminum, to allow a person 105 tooperate the spray device 100 in an unimpeded manner to simulate typicaluse of the spray bottle 100. The shaft 605 may be a hardened precisionshaft constructed of ¼″ O.D. stainless steel. The bearing 610 may belined with various materials to allow the shaft 605 to travel smoothlyand freely, thereby facilitating unimpeded in vitro motion.

In this embodiment, the mounting assembly 320 c is connected to a footassembly 620 via a bracket assembly 625. Screws or other connectionmeans are used to connect the bracket assembly 625 to the mountingassembly 320 c and the foot assembly 620. The foot assembly 620 isadapted to allow the entire assembly 600 to stand in a verticalarrangement such that the spray device 100 is held in a verticalrelationship with the foot assembly 620 and suspended above a surface(e.g., weight measuring scale platform or table top) on which the footassembly 620 rests.

The assembly 600 and spray device 100 may have a predetermined weightfor use on a weight measuring scale that is sensitive enough to measurea change in fluid ejected by the spray device in a single discharge.Accordingly, if the foot assembly 620 is frame-like, weight can beminimized to meet a lightweight criterion. For example, the total weightof the assembly 600 and spray device 100 may be required to be less than200 grams. If even more weight need be removed from the assembly 600,the bracket assembly 625 can also be formed in a frame-like manner, asshown.

FIG. 7 is a side view of the assembly 600 with the spray device 100. Themounting assembly 320 c includes adjustment screws 515 and slots 520 toaccommodate spray devices 100 having different diameters. Similaradjustment means may be provided on the adapter assembly 315 c. Varioustypes of alignment means may be provided to remove motion in across-axis to the actuation axis 505 a (FIG. 5A).

The MDI 400 generally maintains alignment in the actuation axis 505 b.Therefore, the shaft 605 and bearing 610 design is generally unnecessaryfor allowing the transducer 335 to indicate the mechanical relationshipbetween the movable part 405 and the stationary part 410 of the MDI 400without having errors caused by rapid changes in length of the linkage330.

FIG. 8 is an illustration of an automated actuation system 800 thatoperates the spray device 100 in an automated manner. The automatedactuation system 800 includes a compression plate assembly 805 thattravels vertically along a pair of passive, parallel, guide bars 810. Inone embodiment, a drive motor assembly (not shown) drives a belt andpulley assembly (not shown) that drives a drive plate assembly 835 alonga drive rod 830. The drive plate assembly 835 is connected to thecompression plate assembly 805 in this embodiment. In response to upwardforce by the drive plate assembly 835, the compression plate assembly805 presses upward on the stationary part 310 of the spray device 100 toactuate the spray device 100. Alternatively, a clamp (not shown) orother attachment means may be used to attach the stationary part 310 ofthe spray device 100 to the compression plate assembly 805. Embodimentsof automated actuation systems 800 are further described in co-pendingU.S. patent application Ser. No. 10/176,930 entitled, “Precise PositionControlled Actuating Method and System”, filed on Jun. 21, 2002; theentire teachings of which are incorporated herein by reference in theirentirety.

To facilitate engagement of the assembly 600 with the automatedactuation system 800, the adapter assembly 315 c may be configured tofit into a predefined cut-out 823 in the top 825 of the automatedactuation system 800. Also, in this embodiment, the bracket assembly 625is disconnected from the foot assembly 620 to allow for the properinterfacing of the assembly 600 with the automated actuation system 800.

The motor assembly and a portion of the belt and pulley assembly may bedeployed in a housing 820 of the automated actuation system 800. Atleast one processor (not shown) and voltage or current driveamplifier(s) (not shown) may also be deployed in the housing 820. Thedrive amplifier(s) may be used to control drive motor(s) in the drivemotor assembly.

In one embodiment of the automated actuation system 800, the compressionplate assembly 805 includes a force transducer (not shown), such as apiezoelectric transducer, that is positioned to sense actuation force ofthe spray device 100 caused by upward force applied by the compressionplate assembly 805. The force transducer may convert force to an outputsignal (e.g., voltage, current, or charge) in a proportional manner andtransmit the output signal on a cable 815 to a sense amplifier (notshown). The sense amplifier is adapted to receive the output signal andconvert it to a signal, with minimal additional noise, that can besampled and processed by the processor.

Alternative embodiments of the automated actuation system 800 may alsobe employed. For example, the compression plate assembly 805 may includethe drive motor assembly, which may employ linear voice coil motor(s),and the drive amplifier(s) may be in the housing 820. In such anembodiment, the cable 815 carries electrical power signals between thedrive amplifier(s) and motor(s) (not shown) in the compression plateassembly 805. The cable 815 may also include feedback wires to allow forclosed-loop control. Alternatively, the compression plate assembly 805may include all the processing and drive amplifiers necessary fordriving the spray device 100, in which case, the cable 815 carries powerand trajectory signals to the motor(s) and processor(s). Othercombinations of electronics locations and wiring are also possible.

Forms of control that the automated actuation system 800 may use tooperate the spray device 100 are open-loop control, closed-loop control,or combination thereof. A Proportional, Integration and Differentiation(PID) controller (not shown) may be employed to provide smooth operationof the compression plate assembly 805. Alternatively, a digitalcontroller may be employed. The output from the transducer 335 may beused for closed-loop control of the spray device 100 since thetransducer 335 directly measures the effect of the compression plateassembly 805 actuating the spray device 100. Use of open- or closed-loopcontrol may be based on at least one parameter, such as an error budgetassociated with force, acceleration, velocity, position, length ofstroke, or other relevant parameters.

A trajectory input (i.e., an actuation profile) to the compression plateassembly 805 is preferably as close to in vitro actuation of the spraydevice 100 as possible to test the performance of the spray device 100.In this way, the automated actuation system 800 can actuate the spraydevice 100 in a manner that allows for near in vitro test conditions.Such testing allows a drug development company or spray devicemanufacturer to test the performance of the spray device 100. Theautomated actuation system 800 may be used in conjunction with anautomated spray characterization (i.e., spray pattern measurement)system that measures spray pattern, plume geometry, priming andrepriming metrics, and/or other metrics associated with actuation of thespray device 100.

FIGS. 9–17 illustrate a processing system and signals captured orgenerated thereby. The data processing system 900 captures data producedby the transducer 335. The data processing system 900 is typicallydistinct from control electronics associated with the automatedactuation system 800, but data captured, processed, and/or produced bythe data processing system 900 may be transferred to the automatedactuation system 800 for use in automated actuation of the spray device100. Data may be transferred between the data processing system 900 andthe automated actuation system 800 via a local area network (LAN),magnetic disk, optical disk, infrared signals, a Wide Area Network (WAN)such as the Internet, or other signal or data transfer means.

Referring first to FIG. 9, the data processing system 900 includes thetransducer 335, which receives stimuli via the linkage 330 as a functionof the mechanical relationship between the movable part 305 and thestationary part 310. In turn, the transducer 335 indicates themechanical relationship.

A signal conditioner 905 is connected to the transducer 335 and providesan output signal to an amplifier 910. The amplifier is connected to andprovides an output to a data sampler 915. The data sampler 915 isconnected to a processor 920. The processor 920 may output informationrelated to the indication of the mechanical relationship between themovable and stationary parts of the spray device 100 on a display 925and/or transfer data or parameters associated with the data to theautomated actuation system 800.

In operation, the signal conditioner 905 provides low-level signalconditioning of signals affected by a change of state of the transducer335. The signal conditioner 905 may have predetermined knowledge of thetype of transducer 335 with which it is in communication. For example,the signal conditioner 905 may provide a consistent current to thetransducer 335 if the transducer 335 is a potentiometer. In thisexample, the signal conditioner 905 may have internal circuitry (notshown) that measures voltage across the potentiometer to provide ameasurement as a function of a change of state of the potentiometercaused by a change in length of the linkage 330 resulting from motion ofthe movable part 305 with respect to the stationary part 310.

The signal conditioner 905 outputs a smooth representation of thevoltage to the amplifier 910 corresponding to the indication of themechanical relationship between the movable and stationary parts of thespray device 100. A waveform 902 represents an example signal indicatingmotion of the movable part as indicated by the transducer 335. An outputfrom the signal conditioner 905 is shown as a signal 907 that theamplifier 910 amplifies for capture by a data sampler 915. The datasampler, in turn, produces a digitized waveform 917, which is receivedby the processor 920. The processor 920 may process the digitized signal917 for determining, for example, parameters associated with in vitrooperation of the spray device 100.

FIG. 10 is an alternative embodiment of the data processing system 900b. The transducer 335 receives an input of +5 VDC 1005 and an output of0–5 VDC 1010. A data acquisition (DAQ) circuit board 1015 captures theoutput generated by the transducer 335, which in this case is a positiontransducer. Therefore, the output from the transducer 335 directlyrelates to the position of the movable part 305 with respect to thestationary part 310. The DAQ board 1015 may be in communication with ageneral purpose computer in a daughterboard arrangement. The informationcaptured by the DAQ board 1015 may be displayed on a monitor 1020 andcontrolled via a Graphical User Interface (GUI) by either a keyboard1025 or mouse 1030. In this way, a user may provide various parametersand other forms of control to cause the DAQ board 1015 to collect theoutput 1010 from the transducer 335 in a customized manner.

FIG. 11 is a flow diagram of a process that may be employed by the dataprocessing systems 900 a, 900 b. The process 1100 may start byinitializing the software variables in the DAQ board 1015 (step 1105).The process 1100 continues and checks for a status change in user inputparameters (step 1110). Examples of user input parameters are samplingfrequency, scale factors, and voltage output levels from the DAQ board1015 to the transducer 335 (i.e., the input 1005 to the transducer 335).If the input value has not changed (step 1115), the process 1100 checksagain for a status change in user input parameters (step 1110). If theinput value has changed (step 1115), the process 1100 continues tooperate as specified by the user.

The process 1100 may acquire sensor response data and compute actuationparameters (step 1120). The process 1100 may also save a report ofresponse histories, acquisition parameters, and sensor information (step1125). Saving the information may include saving information to aserver, local memory, or portable computer readable medium. The process1100 may also reset all parameters to initial conditions (step 1130).The process 1100 may also quit the program (step 1135) in response touser input. Other processes may also be executed by the process 1100that are different from the examples listed.

FIG. 12 is an example Graphical User Interface (GUI) 1200 in which auser may program input conditions, acquisition parameters, and viewcaptured waveforms and associated parameters. A set of input fields 1205includes information related to materials being tested, and personnelinvolved in the testing, such as manufacturer, drug name, lot/device ID,experiment type (e.g., hand or automated actuation), starting dosenumber, operator, and report path to which the captured data is stored.A second set of inputs 1210 relates to the transducer 335, includingserial number and a calibration table, where the calibration tableallows for input such as gain, dc offset, scale factor, or otherparameters related to the calibration of the transducer 335. Another setof parameters input by the use of the GUI 1200 is a set of acquisitionparameters, such as data acquisition collection time span (e.g., onesecond) and sampling frequency (e.g., 1 kHz).

The GUI 1200 also include a graphics area displays a position plot 1220of the position versus time of the movable part 305 with respect to thestationary part 310. The GUI 1200 displays multiple parameters 1225associated with the position plot 1220. The parameters 1225 in thisembodiment include a hold time of 98 msec, stroke length of 0.50 mm,actuation stroke velocity of 38.49 mm/s, acceleration of 2961.13 mm/s²,return stroke velocity of −35.45 mm/s, and return stroke acceleration of−1772.30 mm/s². In one embodiment, the measured parameters 1225 areautomatically calculated based on the data captured and displayed in theposition plot 1220.

FIG. 13 provides graphical representations of position, velocity, andacceleration. The representations are representative of motion of themovable part 305 with respect to the stationary part 310 in a typicalspray device 100, 400 by in vitro actuation or automated actuation. Aposition curve 1305 is similar to the position curve in the positionplot 1220 of FIG. 12. The position curve 1305 rises during an actuationtime, remains at a position (P_(ACT)) during a hold time 1325, anddecreases from P_(ACT) during a return time 1330. A correspondingvelocity curve 1310 rises to a maximum velocity V_(ACT) halfway duringthe actuation time and decreases back to a zero velocity during the holdtime 1325. The velocity decreases to a maximum negative velocity(V_(RTN)) and returns to zero during the return time 1330.

An acceleration curve 1315 illustrates the corresponding accelerationcurve 1315 to the position curve 1305 and velocity curve 1310. Duringthe actuation time 1320, the acceleration increases and decreases tomaximum accelerations (A_(ACT)). Similarly, during the (+/−A_(ACT))return time 1330, the acceleration decreases and increases to maximumaccelerations (+/−A_(RTN)). The maximum accelerations may be calculatedas an average of the magnitude of +/−A_(ACT) levels, and the maximumreturn accelerations may be calculated as an average of the magnitude of+/−A_(RTN) levels.

Processing to calculate the velocity and acceleration curves fromcaptured position data may be performed in an automated manner. Forexample, a software routine that calculates velocity or accelerationdata from position measurements may use a least squares technique. Anexample of such a routine may use a Savitzky-Golay smoothing anddifferentiation filter that optimally fits a set of data points topolynomials of different degrees. This type of filter is useful forsubstantially reducing noise in a manner better than a point-to-pointdifferentiation technique does. Other smoothing filters and processesmay also or alternatively be employed.

It should be understood that if the transducer 335 is an acceleration orvelocity transducer, integration and/or differentiation techniques maybe used to provide the other motion data, plots, and parameters.

FIGS. 14–17 are plots that were produced by a method to measure handactuation parameters for nasal spray pumps that can be used forautomated actuation. Actuation parameters were measured forrepresentative commercially available spray pumps filled with water. Theaverage actuation parameters were then checked to confirm that theautomation actuation system 800 accurately duplicated the ergonomics ofhand actuation. The actuation parameters were optimized within a workingrange of the hand actuation parameters to obtain shot weight deliveryclosest to the delivery target (e.g., label claim by the pumpmanufacturer).

Methods for producing the plots of FIGS. 14–17 include a hand actuationportion, a congruency test portion, and an optimized automated actuationportion.

Referring first to the hand actuation test portion of the method, threepatients were trained on the method for hand actuation. Three primednasal spray pumps were actuated by hand ten times each by the threepatients. The actuation parameters were measured using a data processingsystem, such as the systems 900 a and 900 b of FIGS. 9 and 10,respectively, and the assembly 600 of FIG. 6. After each actuation,expelled shot weight (i.e., liquid expelled during actuation) wasmeasured and is shown in FIG. 14. A curve for each of the three bottleswas recorded and displayed in the plot 1400 in FIG. 14.

The shot weight performance by hand actuation of the three nasal spraypumps is shown. The shot weight average was 92.6 mg compared to a designdelivery target of 100.2 mg. The standard deviation associated with shotweight was 9.2 mg across all actuations. Bottle 1 (curve 1405) had thehighest standard deviation of 10.6 mg across all actuations.

In the congruency test portion of the method, the average actuationparameters from hand actuation were programmed into the automatedactuation system 800 of FIG. 8. Three primed spray devices 100 wereactuated ten times. A quantitative comparison of the position versustime curves measured by each method is shown in FIG. 15, where the handmeasurements are shown in the heavy-lined curve 1505 and the automatedmeasurements are shown in the light-lined curve 1510 in the plot 1500.Shot weight delivery performance for the three units obtained byautomated actuation is shown in FIG. 16, with each of the curves 1605,1610, and 1615 corresponding to spray bottles 1, 2, and 3, respectively,in the plot 1600.

The shot weight performance by automated actuation of three bottlesusing average actuation parameters (not optimized) is shown. The shotweight average was 76.0 mg. The standard deviation associated with shotweight decreased from 9.2 mg with hand actuation to 5.9 mg across allactuations, using automated actuation, a 35.9% reduction. Bottle 1(represented by curve 1605) had the highest standard deviation of 4.12mg across all actuations.

In the optimized automated actuation portion of the method, three primedunits were each actuated ten times in a series of tests thatindependently varied stroke length, hold time, and Intra Actuation Delay(IAD) within the working ranges previously measured during the handactuation portion of the method. The stroke length was varied from theaverage value minus one standard deviation (“−1σ”) to the maximum strokelength that did not damage the bottle. The hold time was varied from theaverage value −1σ to the point where the shot weight did not increasemore than 10% from previous actuations. The IAD was varied from 30, 15,5, to 1 second(s). The data were analyzed to find the optimum levels forstroke length, hold time, and IAD, where the optimum was defined as thelevel which obtained shot weight closest to the nominal specified value(i.e., label claim of the manufacturer). Using the optimum values, threeprimed units were actuated ten times each to confirm shot weightdelivery. A stroke length of 5.11 mm, hold time of 45.55 ms, and IAD of30 sec provided shot weight delivery performance closest to the nominalspecified value (i.e., label claim of the manufacturer) as shown in FIG.17. Three curves 1705, 1710, and 1715 represent shot weights frombottles 1, 2, and 3, respectively, in the plot 1700.

Shot weight performance using optimized, automated actuation settingswas measured. The shot weight average was 101.9 mg compared to a designdelivery target of 100.2 mg. The standard deviation associated with shotweight decreased from 9.2 mg with hand actuation to 4.5 mg across allactuations using automated actuations, a 51.5% reduction. Bottle 3(represented by curve 1715) has the highest standard deviation of 6.19mg across all actuations.

The results of this process indicates that the automated actuationsystem 800 (FIG. 8) can be used to accurately measure actuationparameters during hand actuation of three nasal spray pumps. Averagehand actuation parameters were programmed into the automated actuationsystem 800, and the position versus time curves show that the actuatoraccurately reproduced the ergonomics of hand actuation. Using theautomated actuation system 800 reduced the standard deviation associatedwith shot weight performance from 9.2 mg to 5.9 mg, a 35.9% reductioncompared to hand actuation. Within the range of hand actuationparameters, the parameters were varied to optimize the shot weightdelivery. The standard deviation associated with shot weight performancewas further reduced from 9.2 mg to 4.5 mg, a 51.1% reduction compared tohand actuation. The average shot weight delivery was within 1.7 mg ofthe target designed delivery value. Determining the actuation parametersmay be done prior to conducting any other in vitro measurements, such asspray pattern, plume geometry, or droplet size distribution, to ensurethat the automated actuation system 800 consistently simulates handactuation during these tests.

FIG. 18A is a model 1800 a of a business environment involving fiveparties associated with drug and drug delivery development, production,packaging, and distribution. The parties include: (1) the Food and DrugAdministration (FDA) 1805, which is a regulatory body, (2) a drugdevelopment company 1810, (3) a spray device manufacturer 1815, (4) adevice actuation characterization supplier 1820, and (5) a third partytest service 1825. This model 1800 a describes approval cycles fordeveloping a drug, packaging the drug for shipping and in vitro use,obtaining approval in multiple cycles, and characterizing the in vitroperformance of spray devices 100, 400 used to deliver the drug,optionally for multiple age groups.

The FDA 1805 is charged with the task of ensuring the drugs are safe forhuman use. A drug development company 1810 develops a drug and obtainsclinical trial data 1830 a, which is sent to the FDA 1805 for purposesof gaining clinical trial approval 1835 a. Once the FDA 1805 grantsclinical trial approval 1835 a, the drug development company moves intoa production phase of the drug. During the production phase, the drugdevelopment company 1810 may use the services of a spray devicemanufacturer 1815, who may also need to undergo clinical trialapprovals.

The spray device manufacturer 1815 manufacturers spray devices 100, 400and may fill the spray devices 100, 400 with the drug and collectclinical trial data 1830 b related to production and/or deliveryparameters. The clinical trial data 1830 b may include chemical analysisdata and/or metrics, such as spray shot weight, plume geometry, and soforth. The clinical trial data 1830 b is sent to the FDA 1805. The FDA1805 reviews the clinical trial data 1830 b and grants clinical trialapproval 1835 b. Once clinical trial approval 1835 b is granted, thedrug development company 1810 and spray device manufacturer 1815 areapproved to produce and distribute the drug in the spray device 100, 400that was granted clinical trial approval 1835 a, 1835 b.

In this cycle of approvals, periodic testing occurs to ensure that whatis being manufactured is within the data criteria of the clinical trialapprovals 1835 a, 1835 b. In other words, the FDA 1805 wants to ensurethat distributed drug products fall within the scope of criteria thatwas deemed to be safe for human use.

In the past, the drug development company 1810 and spray devicemanufacturer 1815 would perform the tests by hand. The problem withperforming the tests by hand is that there is variability in handactuation of spray devices. Thus, automated actuation of the spraydevices 100, 400 is considered to be useful for continued complianceapproval to ensure that the drugs and delivery mechanisms adhere to thecriteria associated with the clinical trial approvals 1835 a, 1835 b.

Not only is automated testing useful for production phases of drugmanufacturing and spray device manufacturing, but automated testing mayalso be used in the clinical trial phases of the drugs. In other words,by using a common automated actuation technique for both the clinicaltrial phase and production phase approval cycles of a drug and spraydevice, consistency can be applied to the clinical trial and productionphases of the drug development and production cycles, thereby offeringthe FDA 1805 an increased level of testing consistency and the consumingpublic an increased level of safety.

Continuing to refer to FIG. 18A, the device actuation characterizationsupplier 1820 receives spray bottles with drugs 1840, optionally fromthe drug development company 1810 or spray device manufacturer 1815,depending on the production arrangement between the two companies. Forexample, the drug development company may purchase spray devices fromthe spray device manufacturer 1815 and fill a bottle or canister withthe drugs. Alternatively, the spray device manufacturer 1815 maypurchase the drugs from the drug development company 1810 and fill thespray bottle or canister associated with the spray devices 100, 400 withthe drug. A third party manufacturer (not shown) may also be involvedand purchase both the drugs and spray devices from each of the companies1810, 1815 and distribute the drug product. In any case, the deviceactuation characterization supplier 1820 may characterize the spraybottle with drug 1840 in a manner consistent with the methods andassembly(s) disclosed above in reference to FIGS. 1–17.

The device actuation characterization supplier 1820 collects anddistributes in vitro actuation data 1845 a, 1845 b to the drugdevelopment company 1810 and spray device manufacturer 1815,respectively. The device actuation characterization supplier 1820 mayalso provide services for in vitro actuation testing, data gathering,and correlating of in vitro hand actuation versus automated actuation ofthe spray devices to provide useful information for continued compliancetesting, and, optionally, initial clinical trial testing.

Using the in vitro actuation data 1845 a, 1845 b, the drug developmentcompany 1810 and spray device manufacturer 1815 may load and run thedata 1845 a, 1845 b in automated actuation systems 1800. Optionally, athird party test service 1825 may be employed to run this testing. Inany case, the drug development company 1810, spray device manufacturer1815, or a third party test service 1825 gathers continued compliancedata 1850 a, 1850 b, and 1850 c, respectively, which is sent to the FDA1805 to receive approval for complying with regulations of continuing toensure that the drugs that are being produced and packaged for use inspray devices 100, 400 are consistent with the original clinical trialapprovals 1835 a, 1835 b. In turn, the FDA 1805 grants continuedcompliance approval 1855 a, 1855 b, or 1855 c to each of the companies,respectively. If the third party test service 1825 performs thecontinued compliance approval testing, then the third party test service1825 sends a notice of approval 1860 to either the drug developmentcompany 1810 or spray device manufacturer 1815, depending on which ofthe companies hires their services.

It should be understood that the third party test service 1825 may bethe device actuation characterization supplier 1820 or a subsidiary ofone or both of the drug development company 1810 or spray devicemanufacturer 1815. Because the lines distinguishing the companiessometimes becomes blurred, it should be understood that a variety ofmodels 1800 a of business environments can be constructed withoutdeparting from the principles of the present invention.

FIG. 18B is a model 1800 b similar to the model 1800 a just described.The model 1800 b includes a computer network 1865, such as the Internet,that is employed to transfer data in data packets, analog or digitalmodulated signals, or other signaling means to share the data among theparties 1805, 1810, 1815, 1820, and 1825. For example, the in vitroactuation data or parameters 1845 a may be transmitted from the deviceactuation characterization supplier 1820 to any of the other parties1805, 1810, 1815, or 1825 via the network 1865 or through use of a datadisk 1870, which may be an optical disk, magnetic disk, or othercomputer readable media.

FIG. 19 is a flow diagram or a process 1900 that embodies the approvalcycles described above. A process 1900 begins with the drug developmentcompany developing a new drug (Step 1905). A determination is madewhether the drug is over-the-counter (OTC) or a prescription drug(1910). If the drug is an OTC drug, then the FDA 1805 grants approvalbased on safety, effectiveness, and so forth in different age groups(Step 1915).

The FDA 1805, in the case of an OTC drug, does not have to grantapproval based on the delivery mechanism (i.e., spray device 100, 400).If, however, the drug is a prescription drug (Step 1910), initial FDAapproval (Step 1920) must be gained in Phases I–III clinical trials,which test for safety, effectiveness of the drug, drug delivery means,and so forth. An automated actuation system 800 may be useful for theinitial FDA approval, described as the clinical trial approvals 1835 a,1835 b in FIGS. 18A and 18B. After gaining initial FDA approval (Step1920), the drug development company 1810 and spray device manufacturer1815 begin the manufacturing phase to produce what was approved in theclinical trials (Step 1925). Optionally, the FDA 1805 and/or drugdevelopment company 1810 may require further testing, includingstability testing (Step 1930), such as product stability over time,temperature, humidity, and so forth.

During the manufacturing cycle, one of the companies 1810, 1815, or 1825may seek continued FDA approval (Step 1935) to gain continued complianceapproval 1855 as described above in reference to FIG. 18A. If thecompany receives continued compliance approval (Step 1940), themanufacturing of the drug and spray device 100, 400, may be allowed tocontinue under FDA 1805 auspices; otherwise, an investigation (Step1945) of the drug and delivery means begins to determine why the datadoes not show the drug or delivery means meets the criteria associatedwith the initial clinical trial approval 1835. Therefore, stabilitytesting (Step 1930) or manufacturing (Step 1925) may fall into theinvestigation cycle. The manufacturing processes (Steps 1925–1945)continue for the lifetime of the drug.

An embodiment of a drug manufacturing process (Step 1925) is shown infurther detail in FIG. 20. Referring to FIG. 20, the process 1925 beginswith the manufacturing of the prescription drug (Step 2005). The drug isbottled in a metered dose spray bottle or canister, or more generically,a spray device 100, 400 (Step 2010). The manufacturer of the drug (e.g.,drug development company 1810 or spray device manufacturer 1815) mayorder the in vitro actuation data associated with operation of the spraydevice (Step 2015) from the device actuation characterization supplier1820. The company performing the compliance testing receives the datafrom the device actuation characterization supplier 1820 and installsthe data into an automated actuation system 800 (FIG. 8) (Step 2020).The manufacturing company collects data for continued complianceapproval (Step 2025), such as through use of a spray measurement system.The process 1925 returns to the process 1900, Step 1925 of FIG. 19 (Step2030).

Continuing to refer to FIG. 20, the steps associated with ordering invitro actuation data (Step 2015) and receiving the in vitro actuationdata (Step 2020) is further described in FIG. 21.

Referring to FIG. 21, a process 2100 begins with the receipt of theorder for the in vitro actuation data from FIG. 20, Step 2015 (Step2105). The process 2100 continues in which the device actuationcharacterization supplier 1820 determines a minimum number of primingstrokes by hand actuation (Step 2110). The process 2100 continues with adetermination of the actuation parameter ranges by hand actuation (Step2115). A determination of an initial estimation of delivery performancecongruency between hand and automated actuation is performed next (Step2120). The process continues in which an adjustment of the automatedactuation parameters to achieve desired shot weight is made, and adetermination of acceptable ranges is made (Step 2125). The process 2100ends (to FIG. 20, Step 2020) with the delivery of the in vitro actuationdata, optionally in a format for use in an automated actuation system(Step 2130).

Each of the steps 2110, 2115, 2120, and 2125 is provided in furtherdetail below in steps 1, 2, 3, and 4, respectively.

Step 1. Determine the minimum number of priming strokes by handactuation.

1.1. Procure the required number of spray pump units filled with drugformulation.

1.2. Select one of the units randomly.

1.3. Measure the weight of the unit on an appropriate balance or scale,and tare the balance with the unit.

1.4. Actuate the unit by hand.

1.5. Record the shot weight data (weight of formulation released duringactuation) for each actuation and tare the balance between actuations.

1.6. Repeat steps 1.2–1.5 for the remaining units.

1.7. Analyze the shot weight data from each unit and determine theminimum number of actuations required to obtain stable shot weightperformance (e.g., the shot weight being within 95–105% of label claim.)

Step 2. Determine the actuation parameter ranges by hand actuation.

2.1. Procure the required number of spray pump units filled with drugformulation from the same lot(s) used in Step 1, above.

2.2. Select a representative group of people to actuate the units byhand. These people should be trained on how to actuate the unitsproperly, and they should be from a population that corresponds to theage and gender group range for which the product is targeted.

2.3. Have each person actuate each unit by hand a representative numberof times and record the position vs. time and shot weight data for eachactuation. The position vs. time data may be generated with anappropriate sensor and will be used to determine the settings requiredby the automated actuation system. The shot weight of each actuation maybe measured by an appropriate analytical balance or scale.

2.4. Calculate the minimum, maximum, average, relative standarddeviation (“RSD”), and standard deviation (σ) values for each of theautomated actuation system parameters plus shot weight, based on theindividual actuation recordings. Additionally, compare the calculatedshot weight values to the manufacturer's specifications, if available.

Step 3. Determine an initial estimation of delivery performancecongruency between hand and automated actuation.

3.1. Procure the required number of spray pump units filled with drugformulation from the same lot(s) used in Step 1.

3.2. Set the actuation parameters on the automated actuation system tothe average values determined in Step 2.

3.3. Prime the units using the minimum number of shots determined inStep 1.

3.4. Actuate each unit with the automated actuation system arepresentative number of times.

3.5. Record the position vs. time profile and shot weight data for eachautomated actuation and tare the balance between shots.

3.6. Compile the overall average shot weights and RSD's for the unitsand compare with those from Step 2.

3.7. Qualitatively compare the position vs. time profiles from hand andautomated actuation. Additionally, statistically compare shot weightsfrom hand and automated actuation. If statistical differences appear,investigate the scope and make recommendations as appropriate.

3.8. The definition for delivery performance congruence will be that themeasured shot weight values will be within ±1σ of the values specifiedby the pump manufacturer.

Step 4. Adjust the automated actuation parameters to achieve desiredshot weight and determine acceptable ranges.

4.1. Procure the required number of spray pump units filled with drugformulation from the same lot(s) used in Step 1.

4.2. Set the actuation parameters on the automated actuation system tothe average values determined in Step 2.

4.3. Prime the units using the minimum number of shots determined inStep 1.

4.4. Automatically actuate each unit a representative number of timesusing the average parameters determined in Step 2.

4.5. Record the position vs. time profile and shot weight data for eachautomated actuation and tare the balance between shots.

4.6. Adjust a single actuation parameter (starting with stroke length)in continuous increments of 10% of the average value and repeat Steps4.4–4.5 until a plateau is reached (10 shot average does not change bymore than ±10% of the previous 10 shot average) or until the adjustedactuation parameter is equal to its average value+2σ.

4.7. Compile the overall average shot weights and determine the adjustedactuation parameter range as follows:

Minimum Minimum value to produce shot weight levels within ±1σ of theaverage from Step 2.

Maximum Maximum value to produce shot weight levels within ±1σ of theaverage from Step 2, up to the average +2σ.

4.8. Repeat the above steps for the other parameters and compile all ofthe results.

While this invention has been particularly shown and described withreferences to preferred embodiments thereof, it will be understood bythose skilled in the art that various changes in form and details may bemade therein without departing from the scope of the inventionencompassed by the appended claims.

For example, the assembly 600 of FIG. 6 illustrates the spray device 100being held in vertical relationship with a foot assembly 620. However,it should be understood that alternative support techniques may beemployed for drug device applications and other applications. Forexample, the spray device 100 may be held at an angle or horizontally,or even up side down. Further, other embodiments of a shaft 605 andbearing 610 assembly may be employed. For example, the shaft and bearingmay be mounted to the spray device 100 as opposed to being in aparallel, off-actuation axis arrangement as shown in FIG. 6. Similarly,the linkage 330 described above as extending through the shaft 605 andlocking to the shaft head 615 by way of passing through the central hole635 through the shaft head 615, may also be clipped onto the bottom ofthe shaft 605 closest to the transducer 335.

The motor(s) that drive the compression plate assembly 805 in FIG. 8 maybe external from the guide bars 810 or drive rod 830, as describedabove, or integral with the guide bars 810 or drive rod 830. Forexample, one or more of the guide bars 810 or drive rod 830 may be athreaded screw and be driven by a motor in a worm-gear arrangement withthe compression plate assembly 805, which has a complementary thread insuch an embodiment. Another example includes a slot in the guide bars810 or drive rod 830 with a drive mechanism located inside that isconnected to a mating assembly on the compression plate assembly 805.Further, the automated actuation system 800 may include a mechanism thatconnects to the mounting assembly 320 c in a manner adapted to actuatethe spray device 100 absent the compression plate assembly 805.

Also, although electrical components (e.g., potentiometer) for measuringdisplacement or motion of the adapter assembly 315 with regard to themounting assembly 320 is described herein, other embodiments oftransducers may be employed, such as optical sensors (e.g.,interferometers) or non-contact electrical sensors, such as hall effectsensors or capacitive probe sensors, where the sensors function in amanner essentially equivalent to a transducer 335. Similarly, although atransducer cable 340 is illustrated in the embodiment of FIG. 6, itshould be understood that infrared or Radio Frequency (RF) means fortransmitting transducer data indicating position or motion between theadapter assembly 315 and mounting assembly 320 may be employed.

With regard to the data collection and processing system of FIG. 9,alternative embodiments may be employed. For example, the system 900 amay not use a signal conditioner 905; instead, the system 900 a may usean amplifier 910 that provides minimal noise or has a signal conditioner905 integral in the amplifier 910. Also, various forms of data samplers915 may be employed. For example, a traditional 12- or 16-bit datasampler 915 may be employed. It should be understood that other datasamplers, including non-traditional data samplers may also be used.

The transducer 335 may have a draw wire with a strokelength/displacement range of 0–1.5 inches. The electrical outputcircuitry for the transducer 335 may form a simple voltage divider withthe output voltage signal scaling linearly with the absolute position ofthe draw wire. In addition, the DAQ board 1015 may have a 5 volt DCoutput that can be used as the input voltage for the transducer 335, andthis sets the output range of the sensor to be 0–5 volts DC,corresponding to 0–1.5 inches of displacement, respectively. Inaddition, this output range is preferably compatible with the inputmeasurement range of the DAQ board 1015. This DAQ board 1015 may be ableto read and record the analog voltage signal 902 from the transducer 335up 10 kHz or more. In addition, the DAQ board 1015 may be designed tooperate in a standard personal computer.

A portable or desktop computer system is typically suitable for use withthe present invention. The computer system preferably works with the DAQboard 1015 and associated control software.

The processor 920 may be a general purpose processor or a specializedsignal processor. Similarly, the data acquisition board 1015 of FIG. 10may be a specialized data acquisition board operating in a computer or amicroprocessor adapted to work within the environment to receive analogor digital information from the transducer 335. For example, thetransducer may be a digital encoder or resolver and provide theinformation directly as a digital word or data stream.

The graphical user interface 1200 of FIG. 12 may be a text basedinterface or other form of interface, such as a touch screen. The usermay be allowed to select various points along the curve(s) alone or incombination with automated data capture and processing techniques, whichinclude selection of various parameters associated with position,velocity, or acceleration.

Control software associated with the present invention may be designedto perform the following functions: (i) record the position vs. timehistory of the compression and return stroke trajectories; (ii) verifythe proper operation of the transducer 335 and DAQ board 1015; and (iii)automatically determine the stroke length of the spray device 100, 400,the velocity and acceleration achieved during the compression and returnstrokes, and the hold time of the stroke (the time spent at the fullycompressed position).

The curves of FIGS. 14–17 are indicated for three users. However, itshould be understood that many more users of the spray device 100, 400may be involved in the testing to make more accurate measurements anddetermine accurate parameters. Further, persons of multiple age groups,sizes, hand sizes, health, hand impairments (e.g., carpal tunnelsyndrome), and other criteria may be used in the testing and actuationcharacterization process.

Image Therm Engineering, Inc.'s (Sudbury, Mass.) SprayVIEW NSx, MDx, andOSx automated actuation systems are examples of automated actuationsystems 800 of FIG. 8 suitable for use with the present invention. Thesesystems allow programming of stroke length, compression and returnstroke velocity and acceleration, and hold time levels. The output fromthe processor 920 may be used directly as inputs to these systems, thusallowing a simple transition from the required exploratory studies toautomated actuation to be achieved and documented. In addition, theassembly 600 could be used simultaneously with these automated systemsto verify their proper operation.

It should also be understood that the FDA 1805 is an example of aregulatory body. Alternatively, depending on the application, theregulatory body may be a different department of the U.S. or foreigngovernment, such as the Department of Defense (DOD), National Instituteof Health (NIH), or a non-governmental body, such as a regulatory bodythat defines paint colors, for example. Moreover, the regulatory bodymay not necessarily “regulate” an industry, but, instead, “suggest” orrecommend certain industry-wide parameters. For purposes of thisapplication, the regulatory body definition covers government andnon-government regulatory bodies as well as non-regulatory bodies perse.

The computer network 1865 of FIG. 18B may be other forms of computernetworks based on different arrangements of the companies 1810, 1815,1820, or 1825, depending on organization of these companies, such as ifthe companies are subsidiaries, sister companies, and so forth.

The processes of FIGS. 19–21 may be different for the drug and drugdelivery industries based on changing rules, regulations, and guidelinesdefined by the regulatory body (e.g., FDA 1805) governing the industry.However, it should be understood that if a different regulatory body isinvolved with this or other processes associated with the clinical trialand continued approval process cycles described herein, the process orsteps may vary without departing from the principles of the presentinvention. Moreover, in different industries, the processes may beindustry dependent and vary accordingly.

It should be understood that any of the data collecting or processingmay be implemented in hardware, firmware, or software. If implemented insoftware, instructions may be stored on computer-readable media, such asmagnetic disk, optical disk, read only memory (ROM), random accessmemory (RAM), loaded on a server and transmitted across a computernetwork, or stored on any other form of computer readable medium. Aprocessor loads the software instructions from the computer-readablemedium and executes the instructions to perform the processes describedherein.

The assembly 600 may be used to record the position vs. timetrajectories achieved during actuation of pharmaceutical spray pumpassemblies and also for other applications. Examples of otherapplications include the following: characterization of glue/caulkingguns, household spray pumps, pressurized spray cans, and pharmaceuticalnasal syringes; testing of robotic actuation of industrial nozzles;and/or actuation of cosmetic spray pumps.

1. A method of servicing companies associated with a spray deviceoperating under guidelines of a regulatory body, the method comprising:capturing in vitro actuation data associated with operation of a spraydevice; and distributing the data to a company associated with an aspectof the spray device for testing the spray device to ensure continuedcompliance with prior approval of the spray device by a regulatory body.2. The method according to claim 1 further including converting the datato parameters and distributing the data in the form of the parameters.3. The method according to claim 1 wherein the spray device includes astationary part and a movable part, and wherein the data includes amechanical relationship between the stationary part and the movable partversus time.
 4. The method according to claim 3 further includingmeasuring position, velocity, or acceleration relationships between thestationary part and the movable part.
 5. The method according to claim 1wherein capturing the in vitro actuation data includes sorting the databased on in vitro age groups.
 6. The method according to claim 1 whereincapturing the in vitro actuation data includes determining a minimumnumber of priming strokes by hand actuation.
 7. The method according toclaim 1 wherein capturing the in vitro actuation data includesdetermining actuation parameter ranges by hand actuation.
 8. The methodaccording to claim 1 wherein capturing the in vitro actuation dataincludes determining an initial estimation of delivery performancecongruency between hand and automated actuation.
 9. The method accordingto claim 8 further including adjusting automated actuation parametersassociated with the automated actuation to achieve a desired shot weightand to determine acceptable ranges.
 10. The method according to claim 1wherein distributing the data includes providing the data in a formatexecutable by a machine configured to actuate the spray device in anautomated manner.
 11. The method according to claim 1 wherein the priorapproval is a clinical trial approval.
 12. The method according to claim1 wherein the company is a drug development company.
 13. The methodaccording to claim 1 wherein the company is a spray device manufacturer.14. The method according to claim 1 wherein the company is a testingservice provider.
 15. The method according to claim 1 wherein theregulatory body is the Food and Drug Administration (FDA).